Efficacy of Cotrimoxazole as a De-escalation Treatment of Ventilator-Associated Pneumonia in Intensive Care Unit

NCT05696093 | Recruiting Phase 3 DMC

• 1 other identifier: APHP220799
• Study Type: interventional
• Target: 628
• Locations: 1 country
• Sites: 30

Brief Summary

Efficacy of cotrimoxazole as a de-escalation treatment for adult patients Ventilator-Associated Pneumonia in intensive care unit Multicentre randomized non-inferiority trial comparing cotrimoxazole to standard antibiotic therapy for enterobacterial VAP

Conditions

Ventilator Associated Pneumonia

Keywords

intensive care unit; de-escalation; cotrimoxazole; Ventilator Associated Pneumonia

Outcome Measures

Primary Outcomes (1)

• To demonstrate that cotrimoxazole is non-inferior to best standard of care for the treatment of VAP in ICU in term of survival at day 28

  Vital status at day 28

  28 days after inclusion

Secondary Outcomes (11)

• To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in term of mortality at day 90

  90 days after inclusion

• To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in IC in terms of mechanical ventilation (MV)-free-days at day 28

  28 days after inclusion

• To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in terms of rate of cure between days 7 and 10

  days 7 and 10 after inclusion

• To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in terms of VAP recurrence

  28 days after inclusion

• To demonstrate that cotrimoxazole is superior to best standard of care for the treatment of VAP in ICU in terms of ICU length of stay

  28 days after inclusion

Study Arms (2)

cotrimoxazole

EXPERIMENTAL

Use of cotrimoxazole for enterobacterial VAP. Posology and modalities of antibiotic administration will be optimized based on most recent recommendations for ICU patient. They will receive the treatment for 28 days or until death or until ICU discharge if its before 28days.

Drug: cotrimoxazole

standard antibiotic therapy

ACTIVE COMPARATOR

Use of standard antibiotic therapy enterobacterial VAP. Posology and modalities of antibiotic administration will be optimized based on most recent recommendations for ICU patient. They will receive the treatment for 28 days or until death or until ICU discharge if its before 28days.

Drug: standard antibiotic therapy

Interventions

cotrimoxazole DRUG

Use of cotrimoxazole therapy for enterobacterial VAP

cotrimoxazole

standard antibiotic therapy DRUG

Use of standard antibiotic therapy for enterobacterial VAP

standard antibiotic therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients hospitalized in an ICU
• Under mechanical ventilation for at least five days
• Microbiologically confirmed VAP preferably on a distal lung sample (bronchoalveolar lavage or protected distal specimen) otherwise endotracheal aspiration
• Enterobacteriaceae susceptible to cotrimoxazole, and for polymicrobial VAP, all bacteria susceptible to cotrimoxazole
• \) Treated for at least 24 hours by an appropriate empiric antibiotic therapy (at least one effective antibiotic from the initiation of treatment for this VAP episode), and for polymicrobial VAP, all bacteria susceptible to empiric antibiotic therapy
• Stability of haemodynamic (stability or decrease in catecholamine dose) and respiratory (stability or improvement of FIO2) parameters

You may not qualify if:

• Haemodynamic instability (increasing dose of a catecholamine in the last 24 hours)
• Contra-indication to cotrimoxazole:
• allergy,
• advanced liver insufficiency,
• renal dysfunction with clearance \<15 mL/min/1.73 m² without hemodialysis
• G6PD deficiency
• history of hypersensitivity to one of the components (in particular, hypersensitivity to sulphonamides
• known macrocytic anemia defined by VGM \>
• treatment with methotrexate
• Infection requiring prolonged antibiotic-therapy (pleural empyema, lung abscess, necrotizing pneumonia, etc…)
• Cystic fibrosis
• Immunosuppression (neutropenia, HIV with CD4 lymphocytes below 200/mm3, immunosuppressive therapy or corticosteroid therapy \>0.5 mg/kg/j before ICU admission)
• Cardiac arrest without awakening
• Moribund state (patient likely to die within 24h)
• Limitation of life support (comfort care applied only) at the time of screening

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (30)

Médecine Intensive Réanimation - Centre Hospitalier Universitaire Amiens-Picardie

Amiens, 80054, France

ACTIVE NOT RECRUITING

Médecine Intensive Réanimation - Centre Hospitalier Universitaire Angers

Angers, 49100, France

ACTIVE NOT RECRUITING

Médecine Intensive Réanimation - Centre Hospitalier Béthune - Beuvry

Béthune, 62660, France

ACTIVE NOT RECRUITING

Réanimation Médico-chirurgicale - Hôpital Avicenne

Bobigny, 93000, France

NOT YET RECRUITING

Médecine Intensive Réanimation - CHU Bordeaux - Hôpital Pellegrin

Bordeaux, 33000, France

ACTIVE NOT RECRUITING

Réanimation Médico-chirurgicale - Hôpital Ambroise-Paré

Boulogne-Billancourt, 92100, France

ACTIVE NOT RECRUITING

Réanimation polyvalente et Unité de surveillance continue - Centre Hospitalier de Cholet

Cholet, 49300, France

ACTIVE NOT RECRUITING

Réanimation Médicale - Centre Jean Perrin - Site Gabriel Montpied

Clermont-Ferrand, 63003, France

ACTIVE NOT RECRUITING

Médecine Intensive Réanimation - Hôpital Louis Mourier

Colombes, 92700, France

ACTIVE NOT RECRUITING

Réanimation polyvalente et surveillance continus - Centre Hospitalier Sud Francilien

Corbeil-Essonnes, 91100, France

ACTIVE NOT RECRUITING

Médecine Intensive Réanimation - Hôpital François Mitterrand

Dijon, 21079, France

ACTIVE NOT RECRUITING

Réanimation Polyvalente - Centre Hospitalier Annecy Genevois

Épagny, 74370, France

NOT YET RECRUITING

Médecine Intensive Réanimation - Centre Hospitalier Départemental Vendée

La Roche-sur-Yon, 85000, France

ACTIVE NOT RECRUITING

Médecine Intensive Réanimation - Hôpital Michallon

La Tronche, 38700, France

ACTIVE NOT RECRUITING

Réanimation Médicale - Hôpital Robert Salengro

Lille, 59037, France

NOT YET RECRUITING

Réanimation médicale - Centre Hospitalier de Longjumeau

Longjumeau, 91160, France

ACTIVE NOT RECRUITING

Réanimation et Surveillance continue - Centre Hospitalier de Melun

Melun, 77000, France

ACTIVE NOT RECRUITING

Médecine Intensive Réanimation - CHRU de Nancy - Hôpitaux de Brabois

Nancy, 54000, France

ACTIVE NOT RECRUITING

Réanimation Médicale et Maladies Infectieuses - Hôpital Laennec

Nantes, 44093, France

NOT YET RECRUITING

Médecine Intensive et Réanimation - Hôpital de la Pitié Salpêtrière

Paris, 75013, France

ACTIVE NOT RECRUITING

Réanimation Médicale - Hôpital de la Pitié Salpêtrière

Paris, 75013, France

RECRUITING

Réanimation Médicale - Hôpital Européen Georges Pompidou

Paris, 75015, France

RECRUITING

Centre Hospitalier Intercommunal Saint-Germain-en-Laye

Poissy, 78003, France

ACTIVE NOT RECRUITING

Médecine Intensive Réanimation - Hôpital René Dubos

Pontoise, 93500, France

ACTIVE NOT RECRUITING

Médecine Intensive Réanimation - Centre Hospitalier Léon Binet

Provins, 77160, France

NOT YET RECRUITING

Médecin Intensive Réanimation - Hôpital Delafontaine

Saint-Denis, 93200, France

NOT YET RECRUITING

Réanimation Polyvalente - Centre Hospitalier Universitaire Nord Saint-Etienne

Saint-Priest-en-Jarez, 42270, France

ACTIVE NOT RECRUITING

Médecine Intensive Réanimation - Nouvel Hôpital Civil

Strasbourg, 67091, France

ACTIVE NOT RECRUITING

Réanimation Polyvalente - Hôpital Sainte Musse

Toulon, 83056, France

ACTIVE NOT RECRUITING

Médecine Intensive Réanimation - Hôpital Bretonneau

Tours, 37000, France

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Central Study Contacts

Damien Roux, MD-PhD

CONTACT

01.47.60.63.29; damien.roux@aphp.fr

Aline DECHANET

CONTACT

01.40.25.78.30; aline.dechanet@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicentre randomized non-inferiority trial comparing cotrimoxazole to standard antibiotic therapy for enterobacterial VAP.

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: January 25, 2023
• Study Start: October 19, 2023
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (30)